Adaptive versus maladaptive right ventricular remodelling

Abstract

Right ventricular (RV) function and its adaptation to increased afterload [RV-pulmonary arterial (PA) coupling] are crucial in various types of pulmonary hypertension, determining symptomatology and outcome. In the course of disease progression and increasing afterload, the right ventricle undergoes adaptive remodelling to maintain right-sided cardiac output by increasing contractility. Exhaustion of compensatory RV remodelling (RV-PA uncoupling) finally leads to maladaptation and increase of cardiac volumes, resulting in heart failure. The gold-standard measurement of RV-PA coupling is the ratio of contractility [end-systolic elastance (Ees)] to afterload [arterial elastance (Ea)] derived from RV pressure-volume loops obtained by conductance catheterization. The optimal Ees/Ea ratio is between 1.5 and 2.0. RV-PA coupling in pulmonary hypertension has considerable reserve; the Ees/Ea threshold at which uncoupling occurs is estimated to be ~0.7. As RV conductance catheterization is invasive, complex, and not widely available, multiple non-invasive echocardiographic surrogates for Ees/Ea have been investigated. One of the first described and best validated surrogates is the ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP), which has shown prognostic relevance in left-sided heart failure and precapillary pulmonary hypertension. Other RV-PA coupling surrogates have been formed by replacing TAPSE with different echocardiographic measures of RV contractility, such as peak systolic tissue velocity of the lateral tricuspid annulus (S'), RV fractional area change, speckle tracking-based RV free wall longitudinal strain and global longitudinal strain, and three-dimensional RV ejection fraction. PASP-independent surrogates have also been studied, including the ratios S'/RV end-systolic area index, RV area change/RV end-systolic area, and stroke volume/end-systolic volume. Limitations of these non-invasive surrogates include the influence of severe tricuspid regurgitation (which can cause distortion of longitudinal measurements and underestimation of PASP) and the angle dependence of TAPSE and PASP. Detection of early RV remodelling may require isolated analysis of single components of RV shortening along the radial and anteroposterior axes as well as the longitudinal axis. Multiple non-invasive methods may need to be applied depending on the level of RV dysfunction. This review explains the mechanisms of RV (mal)adaptation to its load, describes the invasive assessment of RV-PA coupling, and provides an overview of studies of non-invasive surrogate parameters, highlighting recently published works in this field. Further large-scale prospective studies including gold-standard validation are needed, as most studies to date had a retrospective, single-centre design with a small number of participants, and validation against gold-standard Ees/Ea was rarely performed.

Keywords: Cardiac magnetic resonance imaging; Conductance catheterization; Echocardiography; Pulmonary hypertension; Right ventricle; Ventriculoarterial coupling.

Figure 1

Illustration of three stages of RV remodelling in the course of progressing PH: (A) normal RV–pulmonary arterial coupling, (B) homeometric adaptation, and (C) heterometric adaptation. For further details, please see the corresponding sections of the text. Ea, arterial elastance; Ees, end‐systolic elastance; IVC, inferior vena cava; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RV, right ventricular; SVC, superior vena cava.

Figure 2

Schematic representations of (A) a pressure–volume loop of the right ventricle and (B) the conductance catheter positioned in the right ventricle. In the pressure–volume loop schematic, a indicates the closure of the tricuspid valve and end of diastole (shown in green), b indicates the opening of the pulmonary valve and end of the isovolumetric contraction (1), c indicates the closure of the pulmonary valve and end of the ejection phase (2) and systole (shown in orange), and d indicates the opening of the tricuspid valve, end of isovolumetric relaxation (3), and beginning of the filling phase (4). EDP, end‐diastolic pressure; EDV, end‐diastolic volume; ESP, end‐systolic pressure; ESV, end‐systolic volume; SV, stroke volume.

Figure 3

Determination of Ees using (A) the multi‐beat method and (B) the single‐beat method. In the multi‐beat method, the preload is reduced from right to left and the red arrow represents Ees. In the single‐beat method, Pmax is a theoretical value that represents the maximum pressure that could be reached in the right ventricle if the pulmonary valves were closed (i.e. maximum afterload). Pmax is calculated by fitting a sine function, a + b*sin(c*x + d), to the phase of isovolumetric contraction and relaxation of the pressure curve. Ees, end‐systolic elastance; ESP, end‐systolic pressure; Pmax, theoretical isovolumetric maximum pressure; SV, stroke volume.

Figure 4

Echocardiographic estimation of right ventricular (RV)–pulmonary arterial coupling. (A) Schematic of M‐mode‐derived tricuspid annular plane systolic excursion. (B) Schematic of peak systolic velocity of lateral tricuspid annulus (S′). (C) RV fractional area change is the planimetric percentage change of RV end‐diastolic (blue) to end‐systolic (red) area. (D, E) Schematics of speckle tracking‐based strain measurement: percentage of (D) whole RV and (E) RV free wall shortening. (F) Three‐dimensional RV volumetry. (G, H) Echocardiographic estimation of pulmonary arterial systolic pressure, based on (G) translation of peak tricuspid regurgitant velocity into trans‐tricuspid pressure gradient by modified Bernoulli equation and (H) addition of central venous pressure estimated from inferior vena cava diameter and respiratory alteration of inferior vena cava diameter.